Dual-Functionalized Injectable pH-Responsive Hydrogels Loaded with Magnesium Peroxide for the Treatment of Implant-Associated Infection

Abstract

Implant-associated infections frequently complicate orthopedic surgeries, resulting in challenging issues. The current therapy of antibiotic treatment and surgical debridement often leads to drug resistance and bone defect. The development of pH-responsive antimicrobial and pro-osteogenic materials is a promising approach to controlling infections and repairing infected bone defects, especially given the weakly acidic pH of the bacterial infection area. Solid peroxides have the potential to provide a sustained release of hydrogen peroxide (H 2 O 2 ), rendering them applicable for antimicrobial purposes. Additionally, their chemical properties render them inherently responsive to pH. Here, we propose a novel GelBA/PVA/MgO 2 hydrogel composed of gelatin (Gel), benzeneboronic acid (BA), poly(vinyl alcohol) (PVA), and magnesium peroxide (MgO 2 ) with self-healing ability and pH-responsiveness. The borate ester bond formed between PVA and BA is a dynamic chemical bond with properties of dynamic formation and dissociation, making the hydrogel both self-healable and pH-responsive. Meanwhile, the addition of MgO 2 improves the network structure of the hydrogel and gives the hydrogel the ability to perform sustained release of H 2 O 2 and Mg 2+ . Experimentally, the GelBA/PVA/MgO 2 hydrogel exhibits controlled and pH-dependent H 2 O 2 and Mg 2+ release, sustained over time at physiological pH (7.4) and significantly increased at infection pH (5.5). In vitro and in vivo outcomes revealed that this hydrogel is able to inhibit Staphylococcus aureus growth and accelerate bone regeneration, improving bone healing without cytotoxic effects on normal tissues. These findings suggest that the GelBA/PVA/MgO 2 hydrogel is a unique and efficient approach for anti-infection and therapeutic implant-associated infections.

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